1. Field of the Invention
The present invention relates to antimicrobial treatment devices. In particular, the present invention relates to treatment devices that make use of the antimicrobial properties of silver to provide targeted, localized antimicrobial action for dental, periodontal and other treatment purposes.
2. Discussion of Background
The care and treatment of wounds is an important part of health care, incorporating the sometimes-irreconcilable goals of satisfactory outcomes, responsiveness to patient concerns, and cost-effectiveness. Wound healing is a cellular process which is triggered by the occurrence of an injury (as used herein, the terms “wound” and “injury” refer to tissue damage or loss of any kind, including but not limited to infections, cuts, incisions (including surgical incisions), abrasions, lacerations, fractures, contusions, burns, amputations, and so forth). Healing is believed to be controlled by a biophysiological feedback mechanism that monitors the extent of the injury and controls cellular activity in the injured area to produce the types and numbers of cells needed to accomplish a repair.
Many conditions can impact normal healing processes, including impaired circulation, conditions such as diabetes, and infections at the situs of the injury which frequently result in non-healing or slowly-healing wounds, unfavorable outcomes, and increased health care costs. In response to these concerns, many hospitals have established specialized centers to treat non-healing wounds. A wide variety of treatment modalities, including local and systemic antibiotics, antibiotic-impregnated dressings, antibiotic and antifungal compositions, and the like are available for treating infected wounds, slowly-healing wounds, and non-healing wounds. Many of these are used prophylactically in an attempt to forestall infections, which are a growing concern due to the spread of antibiotic-resistant strains of bacteria.
Periodontal disease in particular can be difficult to treat due to these and other factors such as diet, non-optimum dental hygiene (which permits the accumulation of minute food particles in the junction area between the tooth and the gum tissue), lack of dental care (due to lack of access to care and/or reluctance to seek care when needed), localized infections, and systemic conditions. Since the advent of fluoride treatment and the resulting decrease in cavities, periodontal disease has become the single greatest cause of tooth loss in the adult population of the U.S. and other developed countries. It is estimated that over half the adult population of the U.S. has some degree of periodontal disease.
Periodontal disease is characterized by the recession of gum tissue from the bases of the involved teeth in a process which exposes dentine tissue and produces “pockets” of infection that extend along the roots of the teeth. If unchecked, this process eventually results in loosening of the roots in the bone sockets and ultimately loss of the affected teeth. The pathogenesis of periodontal disease is believed to be infection with a variety of bacteria, beginning at the gum line with the formation of plaque (a biofilm consisting of bacteria encased in a mucopolysaccharide material secreted by the bacteria) which acts as an irritant to the underlying tissues. If the plaque is not removed periodically (as by routine cleaning by a trained dental hygienist), this condition becomes chronic and eventually extends into the space formed by the junction between the soft tissue of the gum and the tooth root. The infection results in edema (swelling) and irritation of the gum tissues, further enhancing the infection and permitting its extension into the space between the tooth root and the gum, and ultimately between the tooth and the bone socket.
Presently-available treatments for periodontal disease include the removal of plaque, surgical removal of the infected gum tissue (in a procedure commonly termed “scaling”) and rigorous local treatment (including brushing, flossing, antiseptic mouth washes, and antibiotics). Because local administration of antibiotics frequently produces local tissue sensitivity reactions which worsen the condition, systemic antibiotics are preferred. Disadvantages of antibiotic treatment include the known side effects of many antibiotics, the potential for the development of antibiotic-resistant strains of bacteria, and the resulting need for frequent changes in the antibiotics administered to any particular patient. Such modalities require extended, expensive treatment with frequent patient monitoring. Even after successful treatment, recurrence is common unless the patient follows a rigorous program of dental hygiene and diet (low-carbohydrate diets are sometimes helpful in preventing periodontal disease). Thus, there is a need for alternative treatments to address the growing problem of periodontal disease. Treatment approaches that permit targeted delivery of antibiotics to the affected areas would alleviate the problems associated with the use of systemic antibiotics, and also help those patients who find it difficult or impossible to maintain a rigorous program of dental hygiene.
Silver and other metals are widely used in antimicrobial and antifungal applications, including topical preparations (creams, ointments, etc.) as well as wound dressings. (For purposes of this specification, an “antimicrobial metal” is one with “antibiotic,” “antimicrobial,” “cidal,” “bactericidal” and/or “bacteristatic” properties, broadly defined as a metal that is active against at least one pathogenic microorganism, including but not limited to bacteria, protozoa, fungi, rickettsiae, and viruses. Bactericidal agents kill microorganisms, whereas bacteristatic agents prevent their growth and multiplication.). Silver has good bioactivity against a broad spectrum of microorganisms, at relatively low concentrations, thus, it is perhaps the most widely-used antimicrobial metal. Topical preparations that contain silver or silver compounds—silver nitrate, silver sulfadiazine, colloidal silver compositions, silver-protein compounds such as Argyrol™, and so forth—are widely used in medicine. For example, ointments containing silver sulfadiazine are widely used for the treatment of infected burns.
The effectiveness of silver as an antimicrobial agent is at least partly determined by the delivery system. Most silver compounds that dissociate readily yield cations that are highly toxic to human tissues, and therefore are not considered suitable for medical use. Less-toxic compounds, including silver sulfadiazine cream (widely used in the treatment of burns) and silver nitrate solution, do not dissociate readily. These topical compounds must therefore be re-applied frequently to maintain their clinical efficacy.
Iontophoretic (i.e., electrically-generated) silver ions, which can penetrate more deeply into the tissues than silver ions from topical compounds, have been found to inhibit bacterial and fungal growth in vivo and in vitro at current densities as low as 10 nA/mm2. Silver ions are effective even against antibiotic-resistant strains of bacteria and fungi. Iontophoretic silver treatment is somewhat more effective than treatment with silver compounds, with generally the same spectrum of activity as that of silver nylon. The effects of electrically-generated silver ions are described in a number of publications, including the following: J. A. Spadaro, et al., “Antibacterial Effects of Silver Electrodes with Weak Direct Current,” Antimicrobial Agents & Chemotherapy, Vol. 6, pp. 637–642 (1974); T. J. Berger, et al., “Antifungal Properties of Electrically Generated Metallic Ions,” Antimicrobial Agents & Chemotherapy, Vol. 10, pp. 856–860 (1976); R. O. Becker, et al., “Treatment of Orthopedic Infections With Electrically-Generated Silver Ions,” J. Bone & Joint Surgery, Vol. 60-A, pp. 871–881 (1978)), incorporated herein by reference.
Silver and other metals are used in a number of wound dressings, in the form of pure metal, metal salts, or other compounds. Wound dressings that contain silver or silver compounds are described by McKnight, et al. (U.S. Pat. No. 3,800,792), Weaver, et al. (U.S. Pat. No. 5,218,973), Fabo (U.S. Pat. No. 5,340,363), Klippel, et al. (U.S. Pat. No. 3,830,908), Stowasser (U.S. Pat. No. 2,934,066), and Matson (U.S. Pat. No. 4,728,323). Dressings and devices for the administration of electrical stimulation include those described by Konikoff (U.S. Pat. No. 4,142,521), Rogozinski (U.S. Pat. No. 5,395,398), Silver, et al. (U.S. Pat. No. 4,703,108), D'Alerta (U.S. Pat. No. 5,423,874), Jones (U.S. Pat. No. 4,911,688), Juhasz (U.S. Pat. No. 4,817,594), Seiderman (U.S. Pat. No. 4,767,401), Becker, et al. (U.S. Pat. No. 5,814,094, incorporated herein by reference), and Flick (U.S. Pat. No. 6,087,549).
Many different materials are used for manufacturing wound dressings, surgical gowns and masks, surgical drapes, and like products. Available materials may include flexible, conformable substrates, moisture-absorbing layers, gas-permeable and liquid-impermeable layers, selectively-permeable layers, non-adhering or self-adhering layers, and moisture-absorbing layers, of natural fibers or man-made compositions. Antibacterial agents may be added for therapeutic purposes or to increase the shelf life of the product.
By way of example, Kania (U.S. Pat. No. 5,603,122, incorporated herein by reference) describes a form-fitting sleeve member that incorporates a polymeric cushioning material (most preferably a thermoplastic elastomer, silicon-containing elastomer, or thermoset silicone). Delmore, et al. (U.S. Pat. No. 5,939,339) discloses a bandage having a porous, self-adhering elastic substrate which does not adhere to clothing, hair or skin, and which has a permanent compressive force that is sufficient to hold it in place. Caldwell, et al. (U.S. Pat. No. 5,856,245) describe a polymer composition that is impermeable to liquids, permeable to gases, and impermeable (or selectively permeable) to microorganisms. The fabric can incorporate a wide range of additives including growth factor, wound healing proteins such as collagen, electromagnetic and electrostatic shielding agents, electrically conducting agents, and a variety of antimicrobial agents.
Additional materials are described by Strack, et al. (U.S. Pat. No. 5,681,545), Moretz, et al. (U.S. Pat. Nos. 5,217,782; 5,210,882; 5,297,296), Hagiwara, et al. (U.S. Pat. No. 4,525,410), Seymour (U.S. Pat. Nos. 4,460,369 and 4,340,043). Wound dressings are disclosed by Widemire (U.S. Pat. No. 5,782,788), Lang, et al. (U.S. Pat. Nos. 4,860,737 and 4,753,231), Matson (U.S. Pat. No. 4,728,323), Rawlings, et al. (U.S. Pat. No. 4,657,006), Augurt (U.S. Pat. No. 3,903,882), McKnight, et al. (U.S. Pat. No. 3,800,792), Maeth, et al. (U.S. Pat. No. 3,249,109), and Stowasser, et al. (U.S. Pat. No. 2,934,066). Sims (U.S. Pat. No. 4,638,796) provides a method for dressing a wound with a nonadherent, nonabsorbent, conformable material, followed by an absorbent dressing. An antimicrobial agent may be applied to the material.
Wound dressings and other products may include antimicrobial additives to retard spoilage and increase product shelf life. See, for example, Erami (U.S. No. 5,478,563), Hagiwara, et al. (U.S. Pat. No. 5,413,789), Niira, et al. (U.S. Nos. U.S. Pat. Nos. 4,938,958 and 4,938,955), and Barth, et al. (U.S. Pat. No. 4,376,763). Some products contain leachable antimicrobial compositions, for example, Capelli (U.S. Pat. Nos. 5,326,567 and 4,933,178), Jacobson, et al. (U.S. Pat. No. 5,180,585), Yazaki, et al. (U.S. Pat. No. 5,094,847), Edwards, et al. (U.S. Pat. No. 4,906,466), Leibovich, et al. (U.S. Pat. No. 4,808,402), Laurin, et al. (U.S. Pat. No. 4,603,152), and Romans (U.S. Pat. No. 3,092,552).
Our application Ser. No. 09/431,991, filed Nov. 3, 1999 (“Multilayer Antimicrobial Treatment Device”); the disclosure of which is incorporated herein by reference, describes a multilayer device having at least one layer of a silver-containing fabric that that is effective against sepsis-causing and odor-causing microorganisms, at least one moisture-absorbing layer, and, optionally, an outer, moisture-impermeable and gas-permeable layer that serves as an occlusive barrier for directing fluids to the silver-containing layer. The silver is attached to the fabric in a mechanically stable form that releases ionic silver when wetted. The material can be used for prophylactic and therapeutic care and treatment of skin infections and surface wounds (including surgical incisions), as a wound packing material, and as an adjuvant to conventional deodorants. The device is made of nontoxic, nonhazardous, nonallergenic materials, and is inert until activated by contact with perspiration or other suitable liquid.
Application Ser. No. 60/183,599, filed Feb. 18, 2000 and Ser. No. 60/197,010, filed Apr. 13, 2000, the disclosures of which are incorporated herein by reference, disclose a multilayered antimicrobial composition in sheet form, and articles of manufacture that include the composition. The composition includes a layer of polymeric material and a layer containing an antibacterial metal; in a preferred embodiment, the polymeric material is a gel composition comprising a block copolymer and, optionally, mineral oil; the antibacterial layer is provided by coating the gel composition with silver, incorporating silver into the gel composition, or attaching a silver-containing fabric to the gel composition. The composition itself is durable, nontoxic, nonhazardous, substantially nonallergenic and nonirritating, and inert until activated by contact with a suitable liquid (water, perspiration, wound exudate, hydrocolloid, etc.).
Despite the availability of a variety of wound dressings, antimicrobial compositions, delivery systems (both passive and iontophoretic) for supplying bactericidal metals such as silver to a treatment site, there is a need for simple, versatile, cost-effective devices that provide targeted antimicrobial action for dental (including periodontal), post-surgical, and other applications.